Cnestis ferruginea Vahl ex DC (Connaraceae) downregulates expression of immediate early genes in kainic acid-induced temporal lobe epilepsy in mice
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Emmanuel S. Ojo
Abstract
Objectives
This study investigates the influence of Cnestis ferruginea (CF) on kainic acid (KA)-induced immediate early genes (IEGs) associated with hippocampal sclerosis in temporal lobe epilepsy (TLE) in mice.
Methods
Animals were randomly divided into preventive treatment; vehicle (10 mL/kg, p.o.) or CF (400 mg/kg, p.o.) for three consecutive days before KA (5 mg/kg, i.p.) on days 4 and 5. In the reversal model, KA (5 mg/kg, i.p.) was administered on days 1 and 2 before CF (400 mg/kg) administration on days 3–5. Animals were euthanized on day 5, 6 h after KA exposure in preventive model and 1 h after CF administration in reversal model to estimate markers of IEGs.
Results
KA upregulated the expression of c-Fos protein by 3.32-, 9.45-, 8.13-, and 8.66-fold in the hippocampal CA1, CA2, CA3, and DG regions, respectively. Also, KA elevated inducible nitric oxide synthase protein expression by 10.9-, 10.6-, 9.78-, and 9.51-fold. Besides, mRNA expression of brain-derived neurotrophic factors and heat shock protein was increased by 2.38- and 1.39-fold, respectively, after exposure to KA which were attenuated by CF.
Conclusions
CF attenuated KA-induced IEGs and could be used as an adjunct in TLE.
Funding source: University of Lagos Central Research Grant Committee
Award Identifier / Grant number: CRC/2017/06
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Research funding: This work was supported by the University of Lagos Central Research Grant Committee (CRC/2017/06).
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: The experimental procedure was approved by the Health Research Ethics Committee of the College of Medicine, University of Lagos, Nigeria, with approval number: (CMUL/HREC/01/19/482).
References
1. Pitkänen, A, Sutula, TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol 2002;1:173–81. https://doi.org/10.1016/s1474-4422(02)00073-x.Search in Google Scholar
2. Koyama, R. Dentate circuitry as a model to study epileptogenesis. Biol Pharm Bull 2016;39:891–6. https://doi.org/10.1248/bpb.b16-00125.Search in Google Scholar
3. Ishola, IO, Akindele, AJ, Agbaje, EO, Ochieng, CO, Adeyemi, OO. Anticonvulsant effect of methanolic extract and isolation of active constituents from Cnestis ferruginea Vahl ex DC (Connaraceae). West Afr J Pharm 2014;25:9–19.Search in Google Scholar
4. Ojo, ES, Ishola, IO, Ben-Azu, B, Afolayan, OO, James, AB, Ajayi, AM, et al.. Ameliorative influence of Cnestis ferruginea vahl ex DC (Connaraceae) root extract on kainic acid-induced temporal lobe epilepsy in mice: role of oxidative stress and neuroinflammation. J Ethnopharmacol 2019;243:112117. https://doi.org/10.1016/j.jep.2019.112117.Search in Google Scholar
5. Ishola, IO, Akindele, JA, Adeyemi, OO. Sub-chronic toxicity (90 days) study of the methanol root extract of Cnestis ferruginea. Pharm Biol 2012;50:994–1006.10.3109/13880209.2012.655376Search in Google Scholar
6. Ishola, IO, Akindele, AJ, Adeyemi, OO. Analgesic and anti-inflammatory activities of Cnestis ferruginea Vahl ex DC (Connaraceae) methanolic root extract. J Ethnopharmacol 2011;135:55–62. https://doi.org/10.1016/j.jep.2011.02.024.Search in Google Scholar
7. Ishola, IO, Chatterjee, M, Tota, S, Tadigopulla, N, Adeyemi, OO, Palit, G, et al.. Antidepressant and anxiolytic effects of amentoflavone isolated from Cnestis ferruginea in mice. Pharmacol Biochem Behav 2012;103:322–31. https://doi.org/10.1016/j.pbb.2012.08.017.Search in Google Scholar
8. Ishola, IO, Tota, S, Adeyemi, OO, Agbaje, EO, Narender, T, Shukla, R. Protective effect of Cnestis ferruginea and its active constituent on scopolamine-induced memory impairment in mice: a behavioral and biochemical study. Pharm Biol 2013;51:825–35. https://doi.org/10.3109/13880209.2013.767360.Search in Google Scholar
9. Ishola, IO, Chaturvedi, JP, Rai, S, Rajasekar, N, Adeyemi, OO, Shukla, R, et al.. Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells. J Ethnopharmacol 2013;146:440–8.10.1016/j.jep.2012.12.015Search in Google Scholar
10. Okuno, H. Regulation and function of immediate-early genes in the brain: beyond neuronal activity markers. J Neurosci Res 2011;69:175–86. https://doi.org/10.1016/j.neures.2010.12.007.Search in Google Scholar
11. Herrera, DG, Robertson, HA. Activation of c-fos in the brain. Prog Neurobiol 1996;50:83–107. https://doi.org/10.1016/s0301-0082(96)00021-4.Search in Google Scholar
12. Wu, DM, Zhang, YT, Lu, J, Zheng, YL. Effects of microRNA-129 and its target gene c-Fos on proliferation and apoptosis of hippocampal neurons in rats with epilepsy via the MAPK signaling pathway. J Cell Physiol 2018;233:6632–43. https://doi.org/10.1002/jcp.26297.Search in Google Scholar
13. Binder, DK, Croll, SD, Gall, CM, Scharfman, HE. BDNF and epilepsy: too much of a good thing? Trends Neurosci 2001;24:47–53. https://doi.org/10.1016/s0166-2236(00)01682-9.Search in Google Scholar
14. Rana, A, Musto, AE. The role of inflammation in the development of epilepsy. J Neuroinflammation Res 2018;15:144. https://doi.org/10.1186/s12974-018-1192-7.Search in Google Scholar
15. Zagulska-Szymczak, S, Filipkowski, RK, Kaczmarek, L. Kainate-induced genes in the hippocampus: lessons from expression patterns. Neurochem Int 2001;38:485–501. https://doi.org/10.1016/s0197-0186(00)00101-7.Search in Google Scholar
16. Miettinen, R, Kotti, T, Tuunanen, J, Toppinen, A, Riekkinen, PSr, Halonen, T. Hippocampal damage after injection of kainic acid into the rat entorhinal cortex. Brain Res 1998;813:9–17.10.1016/S0006-8993(98)00915-9Search in Google Scholar
17. Ben-Ari, Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 1985;14:375–403. https://doi.org/10.1016/0306-4522(85)90299-4.Search in Google Scholar
18. Healy, S, Khan, P, Davie, JR. Immediate early response genes and cell transformation. Pharmacol Ther 2013;137:64–77. https://doi.org/10.1016/j.pharmthera.2012.09.001.Search in Google Scholar PubMed
19. Ferkany, JW, Zaczek, R, Coyle, JT. The mechanism of kainic acid neurotoxicity. Nature 1984;308:561–2. https://doi.org/10.1038/308561a0.Search in Google Scholar PubMed
20. Lughetti, L, Lucaccioni, L, Fugetto, F, Predieri, B, Berardi, A, Ferrari, F. Brain-derived neurotrophic factor and epilepsy: a systematic review. Neuropeptides 2018;72:23–9. https://doi.org/10.1016/j.npep.2018.09.005.Search in Google Scholar PubMed
21. Yang, T, Hsu, C, Liao, W, Chuang, JS. Heat shock protein 70 expression in epilepsy suggests stress rather than protection. Acta Neuropathol 2008;115:219–30. https://doi.org/10.1007/s00401-007-0297-3.Search in Google Scholar PubMed
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- Genetic polymorphisms of reproductive hormones and their receptors in assisted reproduction technology for patients with polycystic ovary syndrome
- Minireview
- Influence of GSTM1, GSTT1, and GSTP1 genetic polymorphisms on disorders in transplant patients: a systematic review
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